Photophysical properties of protein conjugates with PDT photosensitizers

Abstract

Photodynamic therapy (PDT) of malignant tumors is based on the property of some photosensitizers to be accumulated by tumour tissues'. On subsequent illumination with light of the wavelength absorbed by these photosensitizers tumour cells can be destroyed. Hematoporphyrin derivative and similar agents presently have some negative features. First, these agents do not possess optimal absorption spectrum. In particular the absorbance in the red region is not very high. Second, the composition of these agents varies for different preparations and with the storage time. Third, they do not possess a sufficient selectivity for malignant cells. Furthermore, they are also accumulated in skin causing its damage upon exposure to light. Thus at present the developing of the effective PDT photosensitizers is of great interest. Recently some of this interest has been focussed on the phthalocyanines (PC). These dyes have sufficient molar extinction coefficient (<10 M1cm1) in red region of optical spectrum (650 700 nm). They are non-toxic. Some of them are effective photosensitizers and produce singlet oxygen. They are relatively easy synthesized and resistant to chemical degradation. PC can have different groups added to the external macrocycle perifery. These groups mainly determine chemical properties and solubility. They offer possibility to bind the dyes to any other molecules, for example, proteins. The properties of naphthalocyanines (NC) are rather similar to the ones of PC, but the most efficient absorption band is in region of 750 - 800 nm. An important problem is to increase the ratio between the level of photosensitizer in malignant and normal tissues. One of the possible solutions is the use of photoimmunotoxins, i.e. conjugates of photosensitizers with monoclonal antibodies (mAb) against cancer antigens or tumor marker. Experiments with immunoglobulin-hematoporphyrin2 and dimetoxyhematoporphyrin3 as well as chiorin e6 conjugates4 showed that they retained both photochemical properties of free dyes and immunological ones of antibodies.